Immunohistochemical Analysis of Inflammatory Cells in Benign and Precancerous Lesions and Carcinoma of the Prostate

Abstract

Objective: Inflammation is an important cause of tumorigenesis in various types of malignancy. Mediators derived from inflammatory cells are associated with cancer proliferation, angiogenesis, and DNA damage. In the present study, we immunohistochemically examined the infiltration patterns of inflammatory cells in benign glands including glandular hyperplasia, and in prostatic intraepithelial neoplasia and adenocarcinoma. Methods: Formalin-fixed, paraffin-embedded tissues were obtained from 100 patients with prostate cancer. All patients underwent radical prostatectomy. We assessed the number of infiltrating T cells (CD3⁺), B cells (CD20⁺, CD79alpha⁺), and macrophages (CD68⁺, CD204⁺) in benign and malignant prostate tumors. Results: CD68⁺ macrophages infiltrated benign glands to a higher extent than those of adenocarcinoma. In contrast, the number of CD204⁺ cells was higher in malignant glands than in benign glands. There was no significant difference in the number of infiltrating T cells between benign and malignant tumors; however, the number of infiltrating B cells was significantly reduced in malignant glands. Conclusions: Inflammation of the prostate may act on prostate carcinomas; particularly that involving M2 macrophage infiltration may play a significant role in prostate carcinogenesis.

Inflammation and prostate cancer: friends or foe?

“…myeloid-derived suppressor cells can limit the efficacy of radiotherapy [53]. Fujii et al [54] assessed the number of infiltrating macrophages and a series of adaptive immune cell populations, including CD3 ? T-lymphocytes, CD20 ?…”

“…They found that macrophages infiltrated benign glands to a higher extent than those of prostate cancer. The authors concluded that inflammation of the prostate may be pivotal on prostate carcinomas, particularly that involving M2-polarized macrophage infiltration [54]. Macrophage inhibitory cytokine-1 (MIC-1), also known as prostate-derived factor (PDF), a molecule of the transforming growth factor-beta (TGF-b) superfamily, has been associated with the progression of various types of cancers, including prostate cancer and found down-regulated in benign prostate hyperplasia [55].…”

Mast Cells as a Potential Prognostic Marker in Prostate Cancer

“…It has been recognized that inflammation plays a role in the development and progression of solid tumors although it still remains unclear whether aggressive disease caused increased inflammation or inflammation caused aggressive disease [20, 21]. Prostate cancer is infiltrated by T- and B-lymphocytes, macrophages, natural killer cells, dendritic cells (DCs), neutrophils, eosinophils, and mast cells (MCs) [22]. MCs (MCs) are recognized as important effectors in Immunoglobulin-E (Ig-E) associated immune responses, and potent effector cells of the innate immune system [23–25].…”

Regulation of prostate cancer progression by the tumor microenvironment

“…[39] Additionally, in these studies the M2 phenotype in the macrophages are associated with higher stage tumors and higher Gleason scores. [40, 41] Interestingly, M2-macrophages are thought to also drive other stromal elements, in particular fibroblasts as described above by enhancing the conversion of quiescent fibroblasts to activated myofibroblasts (aka carcinoma-associated fibroblasts), which synergize to promote prostate carcinogenesis. [42] Targeting macrophages using CSF1-inhibitors to block macrophage migration in murine models of prostate cancer restored sensitivity to androgen blockade[43] and improved the efficacy of radiation therapy.…”